Jonathan Foley

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I enjoy applying my decade of industry ML/AI experience to ambiguous technical problems…

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  • Amazon

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Publications

  • Orthogonal control of expression mean and variance by epigenetic features at different genomic loci

    Molecular Systems Biology

    Using a dual-reporter lentiviral model system, we deconvolved the influence of the promoter sequence to systematically study the contribution of the chromatin environment at different genomic locations in regulating expression noise.

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  • Chromatin accessibility at the HIV LTR promoter sets a threshold for NF-κB mediated viral gene expression

    Variable RelA overexpression demonstrated that the viral genomic location sets a threshold RelA level necessary to induce gene expression. Variable RelA overexpression demonstrated that the viral genomic location sets a threshold RelA level necessary to induce gene expression. However, once the induction threshold is reached, gene expression increases similarly for all integration sites. Furthermore, we found that higher induction thresholds are associated with repressive histone marks and a…

    Variable RelA overexpression demonstrated that the viral genomic location sets a threshold RelA level necessary to induce gene expression. Variable RelA overexpression demonstrated that the viral genomic location sets a threshold RelA level necessary to induce gene expression. However, once the induction threshold is reached, gene expression increases similarly for all integration sites. Furthermore, we found that higher induction thresholds are associated with repressive histone marks and a decreased sensitivity to nuclease digestion at the LTR promoter

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  • HIV Promoter Integration Site Primarily Modulates Transcriptional Burst Size Rather Than Frequency

    Here, we assess the integration context dependence of expression heterogeneity from diverse single integrations of a HIV-promoter/GFP-reporter cassette in Jurkat T-cells. Systematically fitting a stochastic model of gene expression to our data reveals an underlying transcriptional dynamic, by which multiple transcripts are produced during short, infrequent bursts, that quantitatively accounts for the wide, highly skewed protein expression distributions observed in each of our clonal cell…

    Here, we assess the integration context dependence of expression heterogeneity from diverse single integrations of a HIV-promoter/GFP-reporter cassette in Jurkat T-cells. Systematically fitting a stochastic model of gene expression to our data reveals an underlying transcriptional dynamic, by which multiple transcripts are produced during short, infrequent bursts, that quantitatively accounts for the wide, highly skewed protein expression distributions observed in each of our clonal cell populations. Interestingly, we find that the size of transcriptional bursts is the primary systematic covariate over integration sites, varying from a few to tens of transcripts across integration sites, and correlating well with mean expression

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  • A novel magnetic bead bioassay platform using a microchip-based sensor for infectious disease diagnosis

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    New technologies are greatly needed to improve laboratory tests that can be used in point-of-care clinical settings. Here, a biosensor was used to detect micron-scale paramagnetic beads in order to replace the conventional enzymatic label used in ELISAs. This novel biosensor was fabricated through standard complementary metal oxide semiconductor (CMOS) manufacturing and was used to quantify magnetic beads bound to the sensor surface by immunological recognition, analogous to ELISA. CMOS…

    New technologies are greatly needed to improve laboratory tests that can be used in point-of-care clinical settings. Here, a biosensor was used to detect micron-scale paramagnetic beads in order to replace the conventional enzymatic label used in ELISAs. This novel biosensor was fabricated through standard complementary metal oxide semiconductor (CMOS) manufacturing and was used to quantify magnetic beads bound to the sensor surface by immunological recognition, analogous to ELISA. CMOS technology can integrate multiple laboratory functions into the sensor chip, potentially enabling inexpensive, compact and sophisticated diagnostic systems for a number of diseases.

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  • Conformational changes in the solution structure of the dengue virus 5' end in the presence and absence of the 3' untranslated region

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    Dengue virus (DENV) is an approximately 10.7-kb positive-sense RNA virus that circularizes via RNA-RNA interactions between sequences in the 5' and 3' terminal regions. Complementarity between the cyclization sequence (CS) and the upstream AUG region (UAR) has been shown to be necessary for viral replication. Here, we present the solution structure of the 5' end of DENV type 2 in the presence and absence of the 3' end. We demonstrate that hybridization between the 5' and 3' CSs is independent…

    Dengue virus (DENV) is an approximately 10.7-kb positive-sense RNA virus that circularizes via RNA-RNA interactions between sequences in the 5' and 3' terminal regions. Complementarity between the cyclization sequence (CS) and the upstream AUG region (UAR) has been shown to be necessary for viral replication. Here, we present the solution structure of the 5' end of DENV type 2 in the presence and absence of the 3' end. We demonstrate that hybridization between the 5' and 3' CSs is independent of the UAR while the 5' UAR-3' UAR hybridization is dependent upon the 5' CS-3' CS interaction

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  • Predicted hexameric structure of the Agrobacterium VirB4 C terminus suggests VirB4 acts as a docking site during type IV secretion

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    Here, we use a variety of bioinformatics methods to predict that the C-terminal domain of VirB4 (including the Walker A and B nucleotide-binding motifs) is related by divergent evolution to the cytoplasmic domain of TrwB, the coupling protein required for conjugative transfer of plasmid R388 from Escherichia coli. This prediction is supported by detailed sequence and structure analyses showing conservation of functionally and structurally important residues between VirB4 and TrwB

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